ABSTRACT
The selective transition-metal catalyzed C-F bond functionalization of inexpensive industrial fluorochemicals represents one of the most attractive approaches to valuable fluorinated compounds. However, the selective C(sp2 )-F bond carbofunctionalization of refrigerant hydrofluoroolefins (HFOs) remains challenging. Here, we report a nickel-catalyzed selective C(sp2 )-F bond alkylation of HFO-1234yf with alkylzinc reagents. The resulting 2-trifluoromethylalkenes can serve as a versatile synthon for diversified transformations, including the anti-Markovnikov type hydroalkylation and the synthesis of bioactive molecule analogues. Mechanistic studies reveal that lithium salt is essential to promote the oxidative addition of Ni0 (Ln ) to the C-F bond; the less electron-rich N-based ligands, such as bipyridine and pyridine-oxazoline, feature comparable or even higher oxidative addition rates than the electron-rich phosphine ligands; the strong σ-donating phosphine ligands, such as PMe3 , are detrimental to transmetallation, but the less electron-rich and bulky N-based ligands, such as pyridine-oxazoline, facilitate transmetallation and reductive elimination to form the final product.
ABSTRACT
A palladium-catalyzed gem-difluoroallylation of propargyl sulfonates with gem-difluoroallylboron has been developed. The reaction features synthetic simplicity and high functional group tolerance, affording 3,3-difluoro-skipped 1,5-enynes with high efficiency and regioselectivity. In particular, the resulting products can serve as versatile synthons for diversified transformations, having potential applications in medicinal chemistry.
ABSTRACT
Selective functionalization of inactive C(sp3)-F bonds to prepare medicinally interesting aryldifluoromethylated compounds remains challenging. One promising route is the transition-metal-catalyzed cross-coupling through oxidative addition of the C(sp3)-F bond in trifluoromethylarenes (ArCF3), which are ideal precursors for this process due to their ready availability and low cost. Here, we report an unprecedented excited-state palladium catalysis strategy for selective defluoroarylation of trifluoromethylarenes with arylboronic acids. This visible-light-induced palladium-catalyzed cross-coupling proceeds under mild reaction conditions and allows transformation of a variety of arylboronic acids and ArCF3. Preliminary mechanistic studies reveal that the oxidative addition of the C(sp3)-F bond in ArCF3 to excited-state palladium(0) via a single electron transfer pathway is responsible for the C(sp3)-F bond activation.
ABSTRACT
Efficient methods for the dicarbofuntionalization of the cyclic alkenes 2-pyrroline and 2-azetine are limited. Particularly, the dicarbofunctionalization of endocyclic enecarbamates to achieve fluorinated compounds remains an unsolved issue. Reported here is a nickel-catalyzed trans-selective dicarbofunctionalization of N-Boc-2-pyrroline and N-Boc-2-azetine, a class of endocyclic enecarbamates previously unexplored for transition metal catalyzed dicarbofunctionalization. The reaction can be extended to six- and seven-membered endocyclic enamides. A variety of arylzinc reagents and bromodifluoroacetate, and its derivatives, undergo the reaction, providing straightforward and efficient access to an array of pyrrolidine- and azetidine-containing fluorinated amino acids and oligopeptides, which may have applications in the life sciences.
ABSTRACT
Efficient silylation reactions of propargyl epoxides catalyzed by copper catalysts have been developed. Under mild reaction conditions, tri- and tetra-substituted functionalized allenols and alkenes could be selectively obtained in moderate to high yields via tuning the bases and solvents used in the reactions. This work provides straightforward and efficient approaches to the synthesis of multifunctionalized 2,3-allenols and stereodefined alkenes from the same starting material of propargyl epoxides.
